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Garr, E.

Publications and source records attributed to Garr, E..

5 recordsLinked to original sources
bioRxiv2026

Memory erasure by dopamine-gated retrospective learning

Erasing outdated memories is crucial for adaptive behavior. Yet once a cue-outcome association is learned, repeated cue exposure without outcome suppresses conditioned behavior without erasing the underlying memory. This allows rapid behavioral recovery when outcomes are reintroduced. Here, we confirm this limitation for standard "prospective extinction" protocols that present cues without the associated outcome, but show that true memory erasure is achieved by inverting the paradigm: presenting outcomes without associated cues, i.e., "retrospective extinction". We demonstrate that orbitofrontal cortex activity at outcome is necessary for the rapid behavioral recovery following prospective extinction, and that mesolimbic dopamine activity at outcome is necessary for retrospective extinction. These findings reconceptualize extinction mechanisms and suggest complementary strategies to mitigate relapse and erase maladaptive memories.

neuroscience↗
bioRxiv2024

Fentanyl reinforcement history has sex-specific effects on multi-step decision-making

It is commonly thought that drug addiction involves a transition to habitual control of action, where the choice to consume drugs becomes automatized and reflects a failure to deliberate over possible negative outcomes. Determining whether the pursuit of addictive drugs is habitual is hampered by a lack of behavior assessments suitable for use during a bout of actual drug seeking. Therefore, to understand how variable histories of drug reinforcement might affect goal-directed and habitual pursuit of drug, we trained rats to perform a multi-step decision-making task to earn oral fentanyl and sucrose rewards following extensive pretraining with either fentanyl or sucrose. Importantly, this task allowed for independent measurements of goal-directed and habitual choice characteristics during online pursuit of rewards, and habitual choice could be further categorized into perseverative and reward-guided components. Chronic fentanyl led to a bias for reward-guided habitual choice specifically in females, and a high degree of perseveration in both sexes. These behavioral changes after chronic fentanyl pretraining generalized across fentanyl and sucrose seeking. In contrast, acute fentanyl selectively increased perseveration in females, and blunted the gradual within-session improvement in goal-directed choice in both sexes. These results show that chronic fentanyl reinforcement promotes habits that generalize across drug and non-drug reward seeking, and that female rats are especially susceptible to habitual control induced by both chronic and acute fentanyl reinforcement.

animal behavior and cognition↗
bioRxiv2023

Mesostriatal dopamine is sensitive to specific cue-reward contingencies

Learning causal relationships relies on understanding how often one event precedes another. To gain an understanding of how dopamine neuron activity and neurotransmitter release change when a retrospective relationship is degraded for a specific pair of events, we used outcome-selective Pavlovian contingency degradation in rats. Two cues were paired with distinct food rewards, one of which was also delivered in the absence of either cue. Conditioned approach was attenuated for the cue-reward contingency that was degraded. Dopamine neuron activity in the midbrain and dopamine release in the ventral striatum showed a profile of changes in cue- and reward-evoked responding that was not easily explained by a standard reinforcement learning model. An alternative model based on learning causal relationships was better able to capture evoked dopamine responses during contingency degradation, as well as conditioned behavior following optogenetic manipulations of dopamine during noncontingent rewards. Our results suggest that mesostriatal dopamine encodes the contingencies between meaningful events during learning.

neuroscience↗
bioRxiv2019

Chemogenetic inhibition in the dorsal striatum reveals regional specificity of direct and indirect pathway control of action sequencing.

Animals engage in intricate action sequences that are constructed during instrumental learning. There is broad consensus that the basal ganglia play a crucial role in the formation and fluid performance of action sequences. To investigate the role of the basal ganglia direct and indirect pathways in action sequencing, we virally expressed Cre-dependent Gi-DREADDs in either the dorsomedial (DMS) or dorsolateral (DLS) striatum during and/or after action sequence learning in D1 and D2 Cre rats. Action sequence performance in D1 Cre rats was slowed down early in training when DREADDs were activated in the DMS, but sped up when activated in the DLS. Acquisition of the reinforced sequence was hindered when DREADDs were activated in the DLS of D2 Cre rats. Outcome devaluation tests conducted after training revealed that the goal-directed control of action sequence rates was immune to chemogenetic inhibition--rats suppressed the rate of sequence performance when rewards were devalued. Sequence initiation latencies were generally sensitive to outcome devaluation, except in the case where DREADD activation was removed in D2 Cre rats that previously experienced DREADD activation in the DMS during training. Sequence completion latencies were generally not sensitive to outcome devaluation, except in the case where D1 Cre rats experienced DREADD activation in the DMS during training and test. Collectively, these results suggest that the indirect pathway originating from the DLS is part of a circuit involved in the effective reinforcement of action sequences, while the direct and indirect pathways originating from the DMS contribute to the goal-directed control of sequence completion and initiation, respectively.

neuroscience↗